Rozanolixizumab is indicated for the treatment of adults with generalized myasthenia gravis (MG). This retrospective, non-interventional cohort study evaluated adults with MG initiating rozanolixizumab in the USA. Patients were selected from de-identified claims data from the Komodo Healthcare Map® (July 2023–March 2025). Enrolled patients were aged ≥ 18 years with MG diagnosis, ≥ 1 rozanolixizumab medical/pharmacy claim, and continuous enrollment/plan coverage for 12 months (baseline period) before first rozanolixizumab treatment initiation (index date). The follow-up period was from 1 day post-index to last enrollment date. Treatment patterns and healthcare resource utilization (HCRU) were assessed during baseline and follow-up. A second study (July 2023–June 2024) assessed patients for 12 months post-index who had ≥ 1 efgartigimod claim ≤ 12 months prior to index. The main study included 719 patients. Patients with ≥ 365 days since rozanolixizumab initiation (n = 287) started a mean (standard deviation) 2.9 (1.8) treatment cycles in Year 1. Total MG-related HCRU incidence rates per 100 person-years were 88.0 during baseline and 82.9 during follow-up, and 86.2 versus 80.8 for outpatient, 25.6 versus 17.3 for inpatient, and 24.9 versus 14.0 for emergency room visits. Approximately half (53.7
IntroductionParkinson's disease is a progressive neurodegenerative condition; there are no treatments currently available to slow disease progression, and no cure. Scientists are studying new treatments, such as disease-modifying therapies (DMTs), that may help slow progression of Parkinson's. Here, we discuss our approach to initiating a collaboration between industry and the Parkinson's community that explores the needs of people with early-stage Parkinson's and their care partners. The aim was to examine ways to build knowledge for newly diagnosed patients, align on the potential of DMTs and support discussions around any future clinical trial participation.MethodsAn exploratory workshop with patient advisors, patient advocacy groups (PAGs), and industry representatives was conducted to evaluate perceptions and identify challenges related to understanding disease modification in early-stage Parkinson's, including the development of a preliminary DMT narrative. Patients and care partners also completed a DMT perceptions questionnaire and tested the narrative for readability. A Strategic Patient Council (SPC) then guided refinement of the narrative and co-created a knowledge-building guide for the Parkinson's community.ResultsA total of 181 people with Parkinson's and their care partners completed the questionnaire. Of these, 72% strongly agreed on the need for new Parkinson's treatments, yet 59% felt that they lacked sufficient knowledge around symptom progression. Based on these data and feedback from the SPC, which comprised nine people from five PAGs, the DMT narrative was revised, leading to improved health literacy from 40% to 61%, within the 'adequate' range of the Suitability Assessment of Materials tool. The knowledge-building guide, informed by SPC input, incorporated a patient-centric framework and described key elements of living with early-stage Parkinson's, ranging from coping with diagnosis to clinical trial involvement.ConclusionA collaboration between industry and the Parkinson's community enabled successful development of knowledge-building materials tailored for people living with early-stage Parkinson's, empowering them with a clearer understanding of emerging innovative therapies.
Thymidine kinase 2 deficiency (TK2d) (MIM 609560) is an ultra-rare, autosomal recessive mitochondrial myopathy caused by TK2 variants, leading to mitochondrial DNA depletion and/or multiple deletions. People with thymidine kinase 2 deficiency experience progressive myopathy, bulbar weakness and respiratory insufficiency, often losing the ability to walk, eat and breathe independently. Doxecitine and doxribtimine represents the first approved treatment for patients with thymidine kinase 2 deficiency with age of symptom onset ≤12 years by the US Food and Drug Administration and the European Medicines Agency; previously, disease management was limited to supportive care. We investigated the efficacy and safety of pyrimidine nucleos(t)ide therapy in thymidine kinase 2 deficiency. Patients treated with pyrimidine nucleos(t)ides were pooled from retrospective (NCT03701568, NCT05017818) and prospective (NCT03845712) studies and company-supported Expanded Access Programs. Untreated patients were pooled from literature reviews and a retrospective chart review study (NCT05017818). Patient subgroups were stratified by age of thymidine kinase 2 deficiency symptom onset (≤12 years and >12 years). The primary outcome was survival in 50th-percentile matched pairs of treated and untreated patients. Other outcomes included status of developmental motor milestones, ventilatory and feeding tube support, and safety. In total, 218 patients were included (treated: 104; untreated: 114). Baseline demographics and characteristics were comparable between subgroups. Most patients had an age of symptom onset ≤12 years [treated: 82/104 (78.8%); untreated: 93/114 (81.6%)]. In the age-of-symptom-onset-≤12-years subgroup, restricted mean survival time (95% confidence interval) was 29.2 (28.2, 30.3) years over the 30 years after symptom onset for treated patients and 14.4 (11.1, 17.6) years for untreated patients. Loss of ≥1 acquired motor milestone was more frequent before treatment start than after. Substantially more patients regained ≥1 lost motor milestone after treatment start than before. Ventilatory and feeding support were used across all age-of-symptom-onset subgroups, but some patients reduced or discontinued support after starting treatment and fewer patients initiated support after treatment start than before. Most treatment-emergent adverse events (TEAEs) did not lead to discontinuation. The most frequent TEAE was diarrhoea [43/50 patients (86.0%)], which was generally mild or moderate and resolved with dose reduction. Serious TEAEs occurred in 28/50 patients (56.0%); few were considered to be drug related [4/50 (8.0%)]. In total, 3/67 patients (4.5%) experienced a fatal serious TEAE, which were not considered to be drug related. These findings indicate that pyrimidine nucleos(t)ide therapy improves survival and functional outcomes in people with thymidine kinase 2 deficiency, especially those with age of symptom onset ≤12 years, and has an acceptable safety profile.
The endothelial cells of the capillary network in the brain, in conjunction with pericytes and astrocyte end feet, form the blood-brain barrier (BBB). This highly selective cellular barrier helps to protect and maintain brain homeostasis. This barrier function must be circumvented to deliver therapeutics to the brain, a growing need owing to the increasing incidence in neurological disorders in progressively aging populations. Animal models may exhibit species-specific differences in response, ultimately leading to problems with predicting efficacy of treatments in humans, and conventional in vitro models of the BBB face challenges of reproducing cell-cell interactions, the human brain microenvironment, and transporter abundance and type. Microphysiological systems (MPS) and other complex in vitro models aim to address these challenges by combining engineered shear forces coupled with cell biology advancements to create models with greater predictive power, thereby contributing towards the replacement, reduction and/or refinement of animal use (3Rs). Here, we provide an industry perspective on the application of MPS to test drug delivery to the brain, including on newer modalities such as targeted protein degraders, biologics, nanoparticles, and viruses. We also highlight important considerations for MPS model qualification centered on cell sourcing, technological platform, and qualification of functionality. This commentary from members of the Innovation & Quality Microphysiological Systems Affiliate also aims to highlight areas where developers and suppliers can help address gaps in model development.
The present study demonstrates the integration of the linear solvation energy relationship (LSER) concept with machine learning (ML) methodologies to improve the predictive and interpretative capabilities of chromatographic retention modeling. Immobilized artificial membrane (IAM) chromatography was employed as a model biochromatographic system, and an in-house library of 993 structurally diverse compounds, with experimentally determined chromatographic hydrophobicity index of IAM (CHIIAM), was used to train LSER-ML models. LSER descriptors were calculated using Absolv and extended with ionization-state descriptors to evaluate the applicability of the LSER framework for realistic in silico virtual screening scenarios. Several regression algorithms were tested, including linear, neighborhood-based, kernel-based, and ensemble tree-based models. Among them, the support vector regression with the radial basis function kernel (SVR-RBF) demonstrated the most balanced performance across all validation metrics of R 2 train = 0.884, R 2 test = 0.853, and Q 2 cv = 0.811, achieving predictive errors (RMSEtrain = 5.546, RMSEtest = 4.609, and RMSEcv = 6.989) close to the analytical uncertainty. Model interpretability was achieved using SHapley Additive exPlanations (SHAP), which confirmed the mechanistic relevance of the Abraham descriptors and the dominant contribution of hydrophobic volume and hydrogen-bonding properties to IAM retention. Applicability domain was verified with a Williams plot (±3 standardized residuals and leverage threshold h*). The results indicate that the proposed LSER-ML approach provides an interpretable, robust, and generalizable tool for modeling membrane-mimetic chromatographic systems and can be effectively applied in virtual screening and property-based molecular design.
